Glossary

63 terms

5

503A bulk drug substances list503A bulks list, 503A: A list maintained by the United States Food and Drug Administration of bulk substances that may be used in compounding by state-licensed pharmacies under section 503A of the Federal Food, Drug, and Cosmetic Act. Nominated substances are sorted into evaluation categories pending a decision.

A

Aib2-aminoisobutyric acid, alpha-aminoisobutyric acid: A non-proteinogenic amino acid with two methyl groups on the alpha carbon. Its substitution into a sequence constrains local conformation and is one of the structural modifications recorded in a peptide's identity data.
acetate saltacetate form: A peptide preparation in which acetate is the associated counter-ion, usually produced by ion exchange after purification. Salt form changes the molecular weight quoted for a substance, so identity records distinguish the free base from named salts.
acylationacylated, lipidation, fatty acid modification: Covalent attachment of a fatty acid or fatty diacid chain, often through a linker, to a side chain such as the epsilon-amino group of lysine. Acylated peptides bind serum albumin in laboratory binding studies, which is reflected in their measured pharmacokinetic parameters.
aggregationaggregate: Association of peptide molecules into dimers, oligomers or larger particles, which may be reversible or not. Aggregates can alter chromatographic behaviour and assay results, and are one reason solutions are examined for clarity before use in laboratory work.
albumin bindingserum albumin binding: Reversible or covalent association of a molecule with serum albumin, the most abundant plasma protein. It is a design strategy for extending circulating half-life, reported in the literature as measured binding affinities and pharmacokinetic parameters.

C

C-terminal amideamidated, amidation: A peptide whose carboxy terminus has been converted to a primary amide, removing the terminal negative charge. Amidation changes the molecular mass by approximately one unit relative to the free acid and is recorded as a structural modification.
CAS numberCAS registry number, CAS: An identifier assigned by the Chemical Abstracts Service to a specific substance, including distinct numbers for a free base and each of its salts. Because salt forms carry different numbers, a CAS number alone does not establish which form a vial contains.
CosIngcosmetic ingredient database: The European Commission database of cosmetic ingredients, recording the international nomenclature name, reported functions and any restrictions under the Cosmetics Regulation. An entry records ingredient status and is not an authorisation of any finished product.
certificate of analysisCOA, CoA: A document issued for a specific lot recording the tests performed, the methods used, the results obtained and the identity of the testing laboratory. It describes that lot only; a certificate for one lot says nothing about the contents of another.
counter-ioncounterion, salt form: An ion associated with charged groups on a peptide to balance charge in the solid state, commonly trifluoroacetate or acetate. Counter-ions contribute to the mass of a lyophilised sample and can affect its behaviour in biochemical and cell-based work.

E

EU/mgendotoxin units per milligram: The unit in which endotoxin burden is reported relative to the mass of material tested. One endotoxin unit is defined against an international reference standard, so figures are comparable only when the method and the reference are stated.
European public assessment reportEPAR: The published assessment issued by the European Medicines Agency for a centrally authorised medicine, setting out the evidence considered and the decision reached. Withdrawn applications are also published, which is how an abandoned application can be documented.
electrospray ionisation mass spectrometryESI-MS, electrospray: A mass spectrometry method in which a liquid sample is sprayed through a charged capillary to produce gas-phase ions, typically a series of multiply charged states for a peptide. The charge-state envelope is deconvoluted to give a single intact mass.
endotoxinlipopolysaccharide, LPS: Lipopolysaccharide from the outer membrane of Gram-negative bacteria, which can elicit strong responses in cell culture and animal models at very low concentrations. Endotoxin content is reported in endotoxin units per milligram and is a standard release test for research materials used in biological assays.

F

FEFOfirst expiry first out: An allocation rule under which stock with the earliest expiry or retest date is issued first, so that material does not age unnecessarily in a store. It is the default allocation order for lots held for research supply.
Fmocfluorenylmethyloxycarbonyl, Fmoc/tBu: A base-labile protecting group for the alpha-amino function, used with acid-labile side-chain protection in the most common solid-phase synthesis strategy. Its removal is monitored spectrophotometrically, which gives a step-by-step record of coupling efficiency.

G

GHSR-1aghrelin receptor, growth hormone secretagogue receptor: The receptor activated by ghrelin and by synthetic growth hormone secretagogues, distinct from the receptor for growth hormone-releasing hormone. Compounds acting here are classified separately from GHRH analogues in the anti-doping literature.
GIP receptorGIPR, glucose-dependent insulinotropic polypeptide receptor: A class B G protein-coupled receptor activated by glucose-dependent insulinotropic polypeptide, the second incretin receptor. Dual agonists are characterised by their relative potency at this receptor and at the GLP-1 receptor.
GLP-1 receptorGLP-1R, glucagon-like peptide-1 receptor: A class B G protein-coupled receptor activated by glucagon-like peptide-1. It is one of the incretin receptors studied in metabolic pharmacology, and agonist activity at it is characterised in vitro by receptor binding and signalling assays.
glucagon receptorGCGR: A class B G protein-coupled receptor activated by glucagon. Agonist activity at this receptor alongside the two incretin receptors is the defining feature of the triple-agonist class in the published pharmacology literature.
growth hormone-releasing hormoneGHRH, growth hormone releasing factor, GRF: A hypothalamic peptide that stimulates release of growth hormone through its own receptor on pituitary somatotrophs. Analogues of its N-terminal fragment form one of the two structural families covered in this knowledge base.

H

HPLChigh-performance liquid chromatography, liquid chromatography: A separation technique in which a sample is carried by a pressurised liquid mobile phase through a column packed with a stationary phase, so that components elute at different times. It is the standard method for assessing peptide purity and for isolating impurity peaks for further study.
half-lifeelimination half-life, t1/2: The time taken for the concentration of a substance in a defined compartment to fall by half, estimated from concentration-time data in a specific study population and model. Values differ between studies and between species, so the source study is always stated.
hygroscopichygroscopicity: Readily taking up water from the surrounding air. Lyophilised peptide cakes are generally hygroscopic, which is why vials are sealed under an inert headspace and allowed to reach ambient temperature before opening in a laboratory setting.

I

INCIinternational nomenclature of cosmetic ingredients: The standardised naming system used to declare cosmetic ingredients on labels. An INCI name identifies an ingredient for labelling purposes and is assigned independently of any pharmaceutical naming.
ISO/IEC 1702517025, laboratory accreditation: The international standard setting general requirements for the competence of testing and calibration laboratories. Accreditation is granted against a defined scope, so a laboratory may be accredited for some methods and not for others.
in vitroin-vitro: Conducted outside a living organism, for example in cell culture or a cell-free system. Findings from such work describe the model used and do not by themselves establish what happens in an intact organism.
international nonproprietary nameINN: A unique generic name assigned to a pharmaceutical substance by the World Health Organization so that it can be referred to unambiguously worldwide. An INN is a naming decision and is not in itself a statement that a substance is authorised anywhere.

L

LAL assayLimulus amoebocyte lysate, LAL test: An endotoxin test based on the clotting cascade of horseshoe crab amoebocyte lysate, run in gel-clot, turbidimetric or chromogenic formats. Results are traceable to a reference standard endotoxin and are sensitive to interference from the sample matrix.
lotbatch, lot number, batch number: A defined quantity of material produced in one process run and treated as a unit for testing and traceability. Every certificate, stability record and shipment record is tied to a lot number, which is the key that links a vial in hand to its analytical record.
lyophilisationfreeze-drying, lyophilised, lyophilization: Removal of water from a frozen solution by sublimation under reduced pressure, leaving a dry solid. The resulting cake is usually more stable in storage than a solution, and its appearance, residual moisture and reconstitution behaviour are quality attributes of the process.

M

MALDImatrix-assisted laser desorption ionisation, MALDI-TOF: An ionisation method in which a peptide is co-crystallised with a light-absorbing matrix and desorbed by a laser pulse, usually producing singly charged ions analysed by time-of-flight. It tolerates some salt contamination better than electrospray and suits rapid intact-mass checks.
Monitoring ProgramWADA Monitoring Program: A list published alongside the Prohibited List of substances that are not prohibited but whose patterns of use in sport are being observed. Inclusion signals surveillance rather than prohibition.
marketing authorisationMA, product licence: A regulator's decision permitting a specific medicinal product to be placed on the market in a defined territory, on stated terms. It attaches to a product, not to a substance, so a substance may be authorised in one product and in no other.
mass spectrometryMS, mass spec: An analytical technique that ionises molecules and measures their mass-to-charge ratios. For peptides it establishes identity by comparing the measured mass with the mass calculated from the intended sequence and modifications, and can distinguish species that co-elute in chromatography.
monoisotopic massexact mass: The mass of a molecule calculated using the principal isotope of each element, as opposed to the average mass, which weights isotopes by natural abundance. High-resolution instruments report monoisotopic masses; the two figures diverge as molecular size increases.

P

Pharmacy Compounding Advisory CommitteePCAC: The United States Food and Drug Administration advisory committee that reviews nominated bulk drug substances and votes on whether they should be added to the compounding lists. Its votes are advisory; the agency publishes its own conclusions separately.
Prohibited ListWADA Prohibited List: The list published annually by the World Anti-Doping Agency of substances and methods prohibited in sport, organised into classes that take effect on 1 January. Examples within a class are illustrative, and the agency states that absence from the list does not make a substance permitted.
PubChem CIDcompound identifier: The compound identifier used by the PubChem database maintained by the United States National Institutes of Health. Several records can exist for chemically related species, so a record is checked for structure and charge state before its identifiers are relied on.
preclinicalpre-clinical, animal model: Research conducted before, or without, studies in humans, typically in cell systems and animal models. A body of evidence described as preclinical has not been tested in the human setting, which is stated explicitly wherever such literature is summarised here.
prescription-only medicinePOM: A classification in United Kingdom medicines law restricting supply of a medicinal product to a prescription from an appropriate practitioner. The classification applies to medicinal products and is recorded in the relevant statutory instruments.
primary endpointprimary outcome: The pre-specified outcome a clinical study is designed and powered to measure. Results for other outcomes are secondary or exploratory and carry correspondingly weaker inferential weight.
puritychromatographic purity, HPLC purity: The proportion of the chromatographable material in a sample that corresponds to the target peptide, usually expressed as the percentage of total peak area in a reversed-phase HPLC run at a stated wavelength. It describes relative composition among detected species and says nothing about how much peptide a vial contains by mass.

S

SMILESsimplified molecular-input line-entry system: A line notation that encodes a molecular structure as a text string, including stereochemistry when written in its isomeric form. It allows a structure to be transferred between software without a drawing file.
secretagoguegrowth hormone secretagogue, GHS: A substance that stimulates secretion of another substance, used in this knowledge base for compounds that stimulate growth hormone release through the ghrelin receptor rather than the growth hormone-releasing hormone receptor.
solid-phase peptide synthesisSPPS, solid phase synthesis: Assembly of a peptide chain on an insoluble resin support, adding one protected amino acid at a time and washing away excess reagents between steps. The chain is cleaved from the resin and deprotected at the end, then purified chromatographically.
specificationspec, acceptance criteria: The list of tests, analytical procedures and acceptance criteria a material must meet to be released. Results are meaningful only against a stated specification, because the same number can pass one specification and fail another.
summary of product characteristicsSmPC: The approved document describing an authorised medicine's composition, indications, pharmacology and safety information, published in the United Kingdom through the electronic medicines compendium. It is a primary source for the authorised status of a product.

U

UNIIunique ingredient identifier: A ten-character alphanumeric identifier assigned by the United States Food and Drug Administration's substance registration system to a defined substance. Like a CAS number it distinguishes salt and hydrate forms from the parent.

D

deamidationdeamidated: Conversion of an asparagine or glutamine side-chain amide to a carboxylic acid, commonly via a cyclic intermediate, adding approximately one mass unit. It is a frequent degradation route in solution and is pH and temperature dependent.
deletion sequencedeletion peptide, des-peptide: An impurity in which one or more residues are missing from the intended sequence because a coupling step did not go to completion. Deletion sequences are usually close in mass and retention time to the target peptide, so both chromatography and mass spectrometry are needed to detect them.

N

net peptide contentpeptide content, NPC: The mass fraction of a lyophilised sample that is peptide, the remainder being counter-ions, residual water and salts. A sample can be high in chromatographic purity and still contain substantially less peptide by mass than the vial label suggests, which is why the two figures are reported separately.
non-proteinogenic residuenon-coded residue, unnatural amino acid: An amino acid that is not among the twenty encoded by the standard genetic code, such as D-isomers or synthetic analogues. Sequences containing them cannot be written unambiguously in one-letter code, so three-letter notation and a modification list are used instead.

O

oxidationoxidised: Addition of oxygen to susceptible residues, most often methionine, tryptophan or cysteine, adding sixteen mass units per oxygen. It is promoted by dissolved oxygen, light and trace metals, and is a routine degradation product observed in stability studies.

R

racemisationepimerisation, D-isomer: Loss of stereochemical integrity at a chiral centre during synthesis, producing a diastereomeric impurity with the same mass as the target peptide. Because the mass is unchanged, chromatographic separation rather than mass spectrometry is the means of detection.
recombinant factor CrFC: An endotoxin detection method using a recombinant form of the first enzyme in the horseshoe crab clotting cascade, read fluorimetrically. It avoids animal-derived lysate and is recognised in several pharmacopoeias as an alternative to the lysate-based assay.
research use onlyRUO, for research use only: A designation indicating that a material is supplied for laboratory research and has not been manufactured, tested or approved for use in or on humans or animals. It describes the basis of supply and confers no authorisation of any kind.
residual moisturewater content: The water remaining in a lyophilised solid after drying, typically measured by Karl Fischer titration and reported as a percentage by mass. It contributes to the mass of the cake and is one of the factors that govern solid-state stability.
retest dateretest period: The date by which a lot should be re-examined against its specification rather than assumed to remain within it. A retest date differs from an expiry date: material passing retest may continue in use, whereas an expiry date marks the end of the assigned period.
reversed-phase HPLCRP-HPLC, reverse phase HPLC: The most common HPLC mode for peptides, using a non-polar stationary phase such as C18 silica and a polar mobile phase, typically water and acetonitrile with an acidic modifier. Peptides separate mainly by hydrophobicity, with more hydrophobic species eluting later in the gradient.

T

trifluoroacetic acidTFA, trifluoroacetate: An acidic modifier widely used in peptide synthesis and reversed-phase chromatography. Residual trifluoroacetate remains associated with basic residues after purification and is a routine component of lyophilised peptide preparations unless it has been exchanged for another counter-ion.
truncated sequencetruncation: An impurity in which chain assembly stopped early, leaving a shorter peptide. Capping steps during synthesis are designed to terminate unreacted chains deliberately so that these species are easier to separate from the full-length product.